Understanding Longevity V: Does Resveratrol Really Make Me Live Longer?

July 12, 2020

I have a bottle of resveratrol sitting here in my closest.  I stopped taking it. Should I take it.  Does it do any good?  I can only take so many supplements.  Is it worthy of being on the list of the total I can handle?

It does have a role.  Let me see if I can explain it to you so that you understand right where it fits and where it provides you benefit.  Resveratrol blossomed some 20 years ago.  It was Sinclair's lab that brought it out in popularity. He was studying yeast cells to see how long they lived.  Twenty-five generations is a pretty old yeast cell.  It takes a lot of dedication to watch them under a microscope for 25 doublings, so Sinclair even set up a lab at his home so he could pull all-nighters.  To his horror and delight, yeast cells with resveratrol lived up to 35 generations (meaning he got much less sleep).  If they didn't have a SIRT-2 gene, it had no effect.  So resveratrol was activating the SIRT-2 gene.  Remember, the SIRT genes, all 7 of them in humans, are the team responsible for keeping your epigenetic code healthy and youthful.  And also, remember, it is the degradation of your epigenetic code that defines when you die.  Your genetic code is immutable.  Your epigenetic code is essentially the various on and off switches on your histone proteins that instruct your cells what genes to copy and when.  That acts like genetic code.  It tells your cells when to differentiate into different organs when to fight different infections when to start different metabolic processes.  It's your operating system.  Your "Windows 97".  We are only on Windows 10 for computers - our genetic code is way ahead of us, so far.  In essence, the SIRT system of proteins is your "longevity circuit" that is activated when your cells sense metabolic stress.  That's a nice way of saying your cells hunker down and live longer to wait out a lack of calories.  Intense exercise, fasting, calorie reduction are all means of engaging that longevity circuit.  

Where does resveratrol come from?  It's found most richly in stressed grapes.  Dark red ones are best.  Pinor Noir, for example.  White wine doesn't have it because we don't use the skins to make white wine.  Why is stress important?  Sinclair believes there is some natural synchronicity here.  We are talking about stressing your cells by reducing calories to engage the longevity circuit.  Grapes raised on poor sandy soil, with a touch of dry weather and with a bit of early frost have the most resveratrol.  They are plants being stressed.  The compounds they make to help their own longevity circuit activates yeast's longevity circuit and our human longevity circuit.

Other researchers have found the same.  You can stuff mice with a high-calorie diet, but on resveratrol, they still live longer.  When Sinclair first published his resveratrol data, red wine sales all over the world went up 30%.  

The problem with resveratrol is that it doesn't dissolve very well to get absorbed in your stomach. And it isn't really very potent.  That combo means it's not very effective.  You have to drink some 750 glasses of Pinot Noir a day to get the effect of longevity that Sinclair demonstrated on lab mice.  (Some would call that very good news.)

But that's where resveratrol lands.  It was the compound that really opened the floodgates into research into STACs: Sirtuin Activating Compounds.  What chemicals and compounds can we engage to address this disease called aging?  That's what resveratrol started.  There are now 100's of these compounds that work to variable degrees.  As science is prone to do, their names are odd and sound like code:  SRT 1720 or SRT 2104.  But with the discovery that NAD was sirtuin food, and in humans activated all 7 sirtuins, attention to resveratrol shifted to NAD and longevity research was off to the races.  

WWW:  What will work for me.  Should you take resveratrol every day?  Well, if you insist and don't mind gobbling one more capsule, no harm done.  But probably minimal benefit.  You will get about 1-3 mg of resveratrol in each glass of Pinot Noir, and no, you really shouldn't have 750 glasses of Pinot Noir a day.  But if the choice comes down to what pills can you tolerate adding, NAD or NMN is the real winner.  You can find NAD-riboside combined with resveratrol from some suppliers.  And if there is any combination, throw in metformin while your are at it.  850 mg a day of Metformin might be about the right dose.  I've been taking it for over a year now and take it right through my rounds of fast-mimicking dieting where I only eat 800 calories for 5 days. The prevailing admonishment is that you don't do metformin when you are fasting.  

Pop Quiz:  

1.   Where do you find resveratrol in nature?    Answer: the skins of grapes, most abundantly when they are raised in hot dry climates, with a touch of frost, stressing the grapes a little. Red wines are the best with Pinot Noir coming out first.  Nothing in white wine. 

2.  What does resveratrol do in the cell?    Answer: it activates SIRT-2, one of the sirtuin family of epigenetic code protection proteins.  

3.   How much resveratrol should I take as a supplement?    Answer:  If you are going to take it, you need a lot.  Find doses of some 1500 mg a day instead of 750 glasses of Pinot Noir.

4.   If I had to choose between resveratrol and NAD-riboside or NMN, which should I take?     Answer: Hands down, the NAD-riboside or NMN

5.   Back to that bottle on my shelf, should I take it?     Answer:  No, have friends over on your deck and share a glass of Pinot Noir. Tell the resveratrol story and leave it at that.   Remember, in COVID times, keep 6 feet of distance. I found Pinor Noir in single-serving bottles so didn't have to pass a bottle around. Prize-winning flavor?  Well, no.  But ok.  

References:   David Sinclair's Life Span, Nature, Nature